Alteration of enteric monoamines with monoamine receptors and colonic dysmotility in 6-hydroxydopamine-induced Parkinson's disease rats

作者：Zhang Xiaoli; Li Yun; Liu Chenzhe; Fan Ruifang; Wang Ping; Zheng Lifei; Hong Feng; Feng Xiaoyan; Zhang Yue; Li Lisheng; Zhu Jinxia^*

来源：Translational Research, 2015, 166(2): 152-162.

DOI：10.1016/j.trsl.2015.02.003

Constipation is common in Parkinson's disease (PD), in which monoamines (dopamine (DA), norepinephrine (NE), and 5-hydroxytryptamine (5-HT)) play an important role. Rats microinjected with 6-hydroxydopamine (6-OHDA) into the bilateral substantia nigra (SN) exhibit constipation, but the role of monoamines and their receptors is not clear. In the present study, colonic motility, monoamine content, and the expression of monoamine receptors were examined using strain gauge force transducers, ultraperformance liquid chromatography tandem mass spectrometry, immunofluorescence, and Western blot. The 6-OHDA rats displayed a significant reduction in dopaminergic neurons in the SN and a decreased time on rota-rod test and a marked decrease in daily fecal production and fecal water content. The amplitude of colonic spontaneous contraction was obviously decreased in 6-OHDA rats. Blocking D1-like receptor and beta(3)-adrenoceptor (beta(3)-AR) significantly reduced the inhibition of DA and NE on the colonic motility, respectively, whereas the 5-HT and 5-HT4 receptor agonists promoted the colonic motility. Moreover, DA content was increased in the colonic muscularis externa of 6-OHDA rats. The protein expression of beta(3)-ARs was notably upregulated, but 5-HT4 receptors were significantly decreased in the colonic muscularis externa of 6-OHDA rats. We conclude that enhanced DA and beta(3)-ARs and decreased 5-HT4 receptors may be contributed to the colonic dysmotility and constipation observed in 6-OHDA rats.

• 出版日期2015-8
• 单位首都医科大学